Immune system deregulation in hypertensive patients chronically RAS suppressed developing albuminuria

Albuminuria development in hypertensive patients is an indicator of higher cardiovascular (CV) risk and renal damage. Chronic renin-angiotensin system (RAS) suppression facilitates blood pressure control but it does not prevent from albuminuria development. We pursued the identification of protein indicators in urine behind albuminuria development in hypertensive patients under RAS suppression. Urine was collected from 100 patients classified in three groups according to albuminuria development: (a) patients with persistent normoalbuminuria; (b) patients developing de novo albuminuria; (c) patients with maintained albuminuria. Quantitative analysis was performed in a first discovery cohort by isobaric labeling methodology. Alterations of proteins of interest were confirmed by target mass spectrometry analysis in an independent cohort. A total of 2416 proteins and 1223 functional categories (coordinated protein responses) were identified. Immune response, adhesion of immune and blood cells, and phagocytosis were found significantly altered in patients with albuminuria compared to normoalbuminuric individuals. The complement system C3 increases, while Annexin A1, CD44, S100A8 and S100A9 proteins showed significant diminishment in their urinary levels when albuminuria is present. This study reveals specific links between immune response and controlled hypertension in patients who develop albuminuria, pointing to potential protein targets for novel and future therapeutic interventions.Sin financiación4.122 JCR (2017) Q1, 12/64 Multidisciplinary Sciences0.809 SJR (2017) Q2, 4/10 OptometryNo data IDR 2017UE

Rationale and study design of the prospective, longitudinal, observational cohort study “rISk strAtification in end-stage renal disease” (ISAR) study

Background: The ISAR study is a prospective, longitudinal, observational cohort study to improve the cardiovascular risk stratification in endstage renal disease (ESRD). The major goal is to characterize the cardiovascular phenotype of the study subjects, namely alterations in micro-and macrocirculation and to determine autonomic function. Methods/design: We intend to recruit 500 prevalent dialysis patients in 17 centers in Munich and the surrounding area. Baseline examinations include: (1) biochemistry, (2) 24-h Holter Electrocardiography (ECG) recordings, (3) 24-h ambulatory blood pressure measurement (ABPM), (4) 24 h pulse wave analysis (PWA) and pulse wave velocity (PWV), (5) retinal vessel analysis (RVA) and (6) neurocognitive testing. After 24 months biochemistry and determination of single PWA, single PWV and neurocognitive testing are repeated. Patients will be followed up to 6 years for (1) hospitalizations, (2) cardiovascular and (3) non-cardiovascular events and (4) cardiovascular and (5) all-cause mortality. Discussion/conclusion: We aim to create a complex dataset to answer questions about the insufficiently understood pathophysiology leading to excessively high cardiovascular and non-cardiovascular mortality in dialysis patients. Finally we hope to improve cardiovascular risk stratification in comparison to the use of classical and non-classical (dialysis-associated) risk factors and other models of risk stratification in ESRD patients by building a multivariable Cox-Regression model using a combination of the parameters measured in the study

Advanced flavin catalysts elaborated with polymers

A variety of biological redox reactions are mediated by flavoenzymes due to the unique redox activity of isoalloxazine ring systems, which are found in flavin cofactors. In the field of synthetic organic chemistry, the term “flavin” is generally used for not only isoalloxazines but also related molecules including their isomers and some analogues, and those having catalytic activity are called flavin catalyst. Flavin catalysts are typically metal-free, and their catalytic activity can be readily accessed using mild terminal oxidants such as H2O2 and O2; therefore, redox reactions with these compounds have great promise as alternatives to reactions with conventional metal catalysts for the sustainable production of important chemicals. We recently became interested in using polymers for the development of flavin catalysts, especially to improve their practicality and advance the field of catalysis. Here, we summarize our recent research on such flavin-polymer collaborations including the development of facile preparation methods for flavin catalysts using polymers, readily reusable polymer-supported flavin catalysts, and flavin-peptide-polymer hybrids that can catalyze the first flavoenzyme-mimetic aerobic oxygenation reactions

Thiourea-Enhanced Flavin Photooxidation of Benzyl Alcohol

Upon irradiation, flavin oxidises 4-methoxybenzyl alcohol to the corresponding aldehyde using aerial O(2) as the terminal oxidant. We have observed that this reaction is significantly accelerated by the presence of thiourea. A series of thiourea-functionalised flavins has been prepared from flavin isothiocyanates and their photocatalytic efficiencies have been monitored by NMR. The alcohol photooxidation proceeds rapidly and cleanly with high turnover numbers of up to 580, exceeding previously reported performances. A likely mechanistic rationale for the more than 30-fold acceleration of the photo-redox reaction by thiourea has been derived from spectroscopic, electrochemical, and kinetic studies. Thus, thiourea acts as an electron-transfer mediator for the initial photooxidation of 4-methoxybenzyl alcohol by the excited flavins. This mechanism has similarities to electron-relay mechanisms in flavoenzymes, for which cysteine sulfenic acid intermediates are proposed. The observation that thiourea mediates flavin photo-redox processes is valuable for the design of more sophisticated photocatalysts based on Nature's best redox chromophore

Copper-mediated 3-N-Arylation of Flavin

A generally applicable method for the direct 3-N-arylation of flavins using arylboronic acids and copper acetate was developed. The reaction conditions were optimized considering the lability of flavins in basic conditions and thermal heating. Donor- and acceptor-substituted arylboronic acids were used yielding 3-N-arylflavins in moderate to good yields by C(aryl)-N(imide) bond formation. UV and fluorescence measurements indicate an ortho­gonal orientation of the additional aromatic substituent to the flavin ring system. The arene substituent is not electronically coupled to the flavin π-system in the ground state, but electron-rich arene substituents in 3-N position significantly reduce the flavin emission intensity

THE Ba-PROBLEM IN CVD-YBa2 Cu3 O7-[MATH] HTC SUPERCONDUCTORS

The evaporation behaviour of Ba(thd)2 in a CVD-process for HTc-Superconductors is presented. The long-time stability as well as possibilities to increase the evaporation rates by changing the geometry of the evaporator and the process conditions are discussed

HIGH-TC-SUPERCONDUCTORS PREPARED BY CVD

YBa2Cu3O7-δ - deposition experiments were carried out in a cold wall stagnation flow CVD-reactor on single crystalline (100)-oriented SrTiO3-substrates at a total pressure of 10 mbar. As source materials different β-diketonate derivates of yttrium, barium and copper were investigated concerning their volatility and decomposition behaviour. Finally for the YBa2Cu3O7-δ deposition process Y(thd)3, Ba(thd)2 and Cu(thd)2 were used. The evaporation temperatures Tv were 112, 208 and 117 °C respectively. High quality films can be obtained with the c-axis perdendicular to the substrate surface at temperatures higher than 850 °C. The transition temperatures of the coatings are higher than 90 K and the critical current densities are in the order of jc = 106 A/cm2 at 77 K and self magnetic field